Studies outlined are designed to investigate the alterations in small intestinal function in diabetes mellitus and to elucidate the underlying mechanism. Genetically diabetic animals will be used to avoid any potential toxic effects of diabetagenic drugs such as alloxan or streptozotocin. The transport rates of amino acids and carbohydrates in the small intestine of normal and genetically diabetic animals will be determined. Changes in kinetic characteristics of transport such as carrier affinity and maximal capacity and permeability characteristics of isolated brush border membrane vesicles will be evaluated. The effect of diabetes on digestive functions of the intestine will be assessed by determining the changes in levels of digestive enzymes localized in the microvillus membrane and by measuring the hydrolytic capacity of the intact intestine for disaccharides. The relationship of spontaneous diabetes to glycolytic and gluconeogenic enzymes of the intestine will also be investigated. While it is already well known that increased levels of glucagon are associated with diabetes, the role of glucagon in inducing intestinal alterations will be determined. After examining the effect of spontaneous diabetes on intestinal function as outlined above, effects of alloxan or streptozotocin administration to these animals will be investigated to find out whether these drugs have any additional effects on intestinal function.